Toxicology and Investigational Pharmacology, Centocor R&D, R-4-2, 145 King of Prussia Road, Radnor, PA 19087, USA.
Expert Rev Clin Immunol. 2009 Sep;5(5):499-521. doi: 10.1586/eci.09.31.
Monoclonal antibodies (mAbs) are widely used in anti-inflammatory and tumor therapy. Although effective, mAbs can cause a variety of adverse effects. An important toxicity seen with a few mAbs is cytokine-release syndrome (CRS). These mAbs include: alemtuzumab, muromonab-CD3, rituximab, tosituzumab, CP-870,893, LO-CD2a/BTI-322 and TGN1412. By contrast, over 30 mAbs used clinically are not associated with CRS. In this review, the clinical aspects of CRS, the mAbs associated with CRS, the cytokines involved and putative mechanisms mediating cytokine release will be discussed. This will be followed by a discussion of the poor predictive value of studies in animals and the prospects for creating in vitro screens. Finally, approaches to decreasing the probability of CRS, decreasing the severity or treating CRS, should it occur, will be described.
单克隆抗体(mAbs)广泛用于抗炎和肿瘤治疗。尽管有效,但 mAbs 可引起多种不良反应。少数 mAbs 可见细胞因子释放综合征(CRS)。这些 mAbs 包括:阿仑单抗、莫罗单抗-CD3、利妥昔单抗、托西珠单抗、CP-870,893、LO-CD2a/BTI-322 和 TGN1412。相比之下,临床上使用的 30 多种 mAbs 与 CRS 无关。在本次综述中,将讨论 CRS 的临床特征、与 CRS 相关的 mAbs、涉及的细胞因子和介导细胞因子释放的假定机制。接下来将讨论动物研究的预测值较差的问题以及体外筛选的前景。最后,将描述降低 CRS 发生概率、降低严重程度或治疗 CRS 的方法。